Adiponectin is an adipocyte-derived, antidiabetic, antiatherogenic adipocytokine that is present in serum as 3 isoforms. Decreased plasma adiponectin levels are closely associated with the severity of nonalcoholic fatty liver diseases. This study was designed to elucidate a role of adiponectin and its mediator adenosine monophosphate-activated protein kinase (

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Background: Relationship between amyloid fibrils and amorphous aggregates has not yet been elucidated. Results: A competitive mechanism of amyloid fibrillation and amorphous aggregation reproduced the observed aggregation kinetics of ␤ 2 -microglobulin. Conclusion: Apparent complexities in amyloid fibrillation are explained assuming supersaturation-limited crystal-like amyloid fibrils and unlimited glass-like amorphous aggregates. Significance: Linkage of the kinetics of protein aggregation and a conformational phase diagram improves the understanding of protein aggregation.

Background: Aggregation and fibrillation of amyloid ␤ peptides (A␤) in lipid bilayers lead to membrane disruption. Results: Small vesicles accelerated A␤ fibrillation, whereas large vesicles promoted amorphous aggregation. Conclusion: Moderate membrane-curvature-dependent interaction is an important factor for A␤ aggregation. Significance: Two types of membrane binding, one leading to amyloid nucleation and the other to non-productive binding, may be common to various amyloidogenic proteins.

The use of the weight loss aids Chaso and Onshido may be associated with acute liver injury. N-nitroso-fenfluramine is a possible hepatotoxic ingredient.

Cancer-associated fibroblasts contribute to cancer progression that is caused by epithelial-mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor-promoting cancer stroma. Here we report that a-smooth muscle actin-positive myofibroblast-like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC-derived myofibroblasts function to maintain tumorinitiating stem cell-like characteristics, including augmenting expression levels of various stemness-associated genes, enhancing sphere-forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both c-secretase inhibitor and siRNA directed against Jagged-1 attenuated MSC-associated E-cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC-derived myofibroblasts play important roles in regulating EMT and tumor-initiating stem cell-like properties of pancreatic cancer cells through an intermediating Notch signal. (Cancer Sci 2013; 104: 157-164) D uring tumor progression, epithelial-mesenchymal transition (EMT) contributes considerably to the malignant characteristics of tumors such as local invasion and distant metastasis.(1,2) Epithelial-mesenchymal transition has recently been reported as the key phenomenon that tightly regulates the stem cell-like characteristics of both normal and malignant cells. (3,4) Side population (SP) technology has been widely used to isolate the stem cell-enriched fraction in a variety of tissue. Side population cells are detected by their own ability to efflux Hoechst33342 dye through an ATP-binding cassette membrane transporter. We recently found that SP cells from pancreatic cancer cells are highly responsive to transforming growth factor-b (TGF-b)-mediated EMT, invasion, and metastasis.(5) Our results suggest that SP cells are enriched with cells that undergo mesenchymal-epithelial transition (MET) after TGF-b-associated EMT. Thus, our results indicated that an EMT ⁄ MET conversion is tightly linked to malignant potential in pancreatic cancer, such as invasion ⁄ metastasis. However, the mechanisms by which the EMT ⁄ MET status is regulated within a tumor in vivo remains undetermined.The tumor microenvironment consists of various stromal cells, including tumor-associated fibroblasts, endothelial cells, pericytes, adipocytes, and immune cells.(6) Among these cell types, cancer-associated fibroblasts (CAFs) and/or myofibroblasts have been recently implicated in regulating tumor progression, invasion, and metastasis. (7,8) Cancer-associated fibroblasts and myofibroblasts secrete a number of important inflammatory mediators, including MMP-2, -3, and -9, that can alter the stromal ECM and potentiate invasion, cell motility, and metastasis.

Background and Aims: Alcoholic liver disease continues to be a major health problem with respect to both morbidity and mortality. To understand the clinical syndromes of alcoholic liver disease, this review highlights the papers on both clinical and basic research of alcoholic liver disease, especially on steatosis, alcoholic hepatitis and fibrosis. Methods: The various forms of alcoholic liver disease are described, and knowledge about the clinical and pathophysiological features of different stages of alcoholic liver disease are summarized. Results: Clinical studies combined with basic research have established a spectrum of alcoholic liver disease from steatosis to steatohepatitis, fibrosis, and cirrhosis. New insights into the pathogenesis of alcoholic liver disease include the key roles of the excess production of cytokines, reactive oxygen species, and the shortage of protective mediators, including adiponectin. Conclusion: These new insights will lead to new specific therapies for the treatment of alcoholic hepatitis and alcoholic liver fibrosis.

Acute ethanol exposure induces oxidative stress and apoptosis in primary rat hepatocytes. Previous data indicate that the mitochondrial permeability transition (MPT) is essential for ethanol-induced apoptosis. However, the mechanism by which ethanol induces the MPT remains unclear. In this study, we investigated the role of Bax, a proapoptotic Bcl-2 family protein, in acute ethanol-induced hepatocyte apoptosis. We found that Bax translocates from the cytosol to mitochondria before mitochondrial cytochrome c release. Bax translocation was oxidative stress dependent. Mitochondrial Bax formed a protein complex with the mitochondrial voltage-dependent anion channel (VDAC). Prevention of Bax-VDAC interactions by a microinjection of anti-VDAC antibody effectively prevented hepatocyte apoptosis by ethanol. In conclusion, these data suggest that Bax translocation from the cytosol to mitochondria leads to the subsequent formation of a Bax-VDAC complex that plays a crucial role in acute ethanol-induced hepatocyte apoptosis.